Abstract 19290: The Mitochondrial Derived Peptide Humanin Protects the Heart From Age-Related Fibrosis
Introduction: Aging is associated with myocardial fibrosis and reduced performance. The mitochondrial derived peptide (MDP) humanin (HN) has been previously demonstrated to have myocardial protection properties. Endogenous HN levels, and consequently its protective effects, fall with age. HN analogs, such as HNG, have beneficial effects on the cardiovascular system, but their role in protecting the heart from age-induced fibrosis has not yet been demonstrated. The current study was designed to test the hypothesis that chronic replenishment of HN by administration of HNG can attenuate the development of age-induced cardiac fibrosis in mice.
Methods: Thirteen C57Bl/6 female mice were divided into 3 groups. Young mice (n=5) were euthanized at 20 weeks old. Additional 18-months old mice were randomized to untreated (Old, n=3) or treated with HNG (Old + HNG, n=5, 4mg/kg/Bw IP) for 14 months. Old mice were euthanized at 32 months of age and hearts harvested to evaluate tissue collagen content with Picrosirius Red staining and test TGF-β1 immunohistochemistry, both quantified blindly.
Results: Old mice showed an increase in fibrotic area compared to young mice (p<0.0001, fig. 1A). Compared to untreated Old mice, Old + HNG showed a significant decrease in fibrosis (p<0.0001) to levels similar to those observed in control young mice (p=0.99). Old mice also showed increased immunoreactivity of TGF-β1 compared to young mice (p=0.001, fig. 1B), whereas in HNG-treated old mice TGF-β1 immunoreactivity markedly decreased (p<0.0001 vs. untreated old mice) to levels similar to those observed in young mice (p=0.46).
Conclusions: HNG treatment resulted in a remarkable reversal of age-induced cardiac fibrosis and TGF-β1 immunoreactivity in mice, potentially by compensating for the physiologic age-induced loss of endogenous HN, and thereby restoring its protective cardiovascular actions. Our data suggests a possible role of HN in prevention of cardiac aging.
Author Disclosures: S. Delrio: None. K. Yen: None. H.H. Mehta: None. P. Cohen: Consultant/Advisory Board; Modest; CohBar Inc. L.O. Lerman: Research Grant; Modest; Stealth Biotherapeutics, Incorporated. Research Grant; Significant; Recombinetics, Inc. A. Lerman: Consultant/Advisory Board; Modest; CohBar.
- © 2016 by American Heart Association, Inc.